Co-administration of oxycodone and morphine and analgesic synergy re-examined.

The paper by Grach et al. [1] in the Journal addresses the little explored potential benefit of combination opioids in analgesia. Compared with a published study documenting oxycodone-morphine synergy in rats [2], the antinociception study by Grach et al. in healthy subjects has significant design limitations to support their conclusions. In rats, antinociception dose–response curves were produced for each of oxycodone and morphine for the relief of noxious thermal pain [2]. Baseline responses increased 3-fold and antinociceptive ED 50 doses of oxycodone and morphine were 2.8 and 8.5 mg kg 1 , respectively. These ED 50 values agreed with previously published data [3]. Dose–response curves employing oxycodone:morphine combination at ratios of 3 : 1, 1 : 1 and 1 : 3 relative to the morphine or oxycodone ED 50 alone, were constructed. Marked antinociceptive synergy was demonstrated using isobolographic analysis and validated by using selective antagonists for each of the combination components. In their study, Grach et al. compared oral doses of 0.5 mg kg 1 morphine or 0.5 mg kg 1 oxycodone with 0.25 mg kg 1 morphine combined with 0.25 mg kg 1